Effect of almond consumption on iron status in inflammatory states

炎症状态下食用杏仁对铁状态的影响

• 批准号: 10439093
• 负责人: Seth Armah
• 金额: $ 44.72万
• 依托单位: UNIVERSITY OF NORTH CAROLINA GREENSBORO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-15 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10439093
• 关键词: Academic Research Enhancement Awards; Adverse effects; Affect; Aging; Analysis of Variance; Anemia; Anemia due to Chronic Disorder; Antioxidants; Blood Transfusion; C57BL/6 Mouse; Calories; Chronic; Chronic Disease; Cognition; Consumption; Data; Diet; Drug Targeting; Elderly; Erythrocytes; Erythropoietin; Fat-Restricted Diet; Fatty acid glycerol esters; Goals; Health; Hematology; Hemoglobin; High Fat Diet; Hospitalization; Immunity; Impaired cognition; Impairment; Individual; Inflammation; Inflammatory; Intake; Intention; Interleukin-6; Intervention; Intravenous; Iron; Lead; Macrophage Activation; Malignant Neoplasms; Measurement; Measures; Modeling; Mus; Nutritional Study; Obesity; Persons; Plasma; Population; Populations at Risk; Production; Productivity; Proteins; Quality of life; Randomized; Recurrence; Red Blood Cell Count; Research; Rheumatoid Arthritis; Risk; Source; Suggestion; System; Testing; Therapeutic; Time; Transfusion; Vitamin E; Work; alpha Tocopherol; base; cell injury; copper zinc superoxide dismutase; dietary approach; dietary control; falls; gut microbiome; gut microbiota; hepcidin; improved; inflammatory marker; iron deficiency; iron supplementation; macrophage; microbial; microbiome composition; mortality; mouse model; oxidative damage; premature; prevent; training opportunity; undergraduate student

Project Summary/Abstract Anemia of inflammation (AI) is the second most prevalent form of anemia. It is caused by chronic inflammation associated with aging and chronic diseases such as cancer and rheumatoid arthritis. While people with AI have sufficient body iron, increased sequestration due to elevated concentration of the protein hepcidin leads to insufficient circulating iron for red blood cell synthesis. AI is also exacerbated by the destruction of red blood cells (RBCs) by macrophages due to inflammation. Unfortunately, current therapies, including blood transfusion, do not reduce the elevated concentrations of hepcidin; furthermore, transfusion increases risk of excess iron, which can cause adverse effects. While experimental drugs targeting hepcidin are being developed, their long- term adverse effects are not known, warranting new non-pharmaceutical approaches. Our long-term goal is to identify dietary approaches for mitigating AI. Consumption of almonds may mitigate AI by different mechanisms; these include (i) reducing inflammation, (ii) altering the gut microbiome composition, and (iii) improving robustness of RBCs by increasing their vitamin E content, which protects them from oxidative damage. In this proposed R15 study, we will test the overall hypothesis that almond consumption will improve iron status in inflammatory states, using obese and aging mice. We chose these mouse models because both conditions are associated with inflammation, increased hepcidin, and impaired iron status markers. Our preliminary 8-week study using a mouse model of obesity provided suggestive evidence that regular almond intake reduced hepcidin and improved iron concentrations in plasma; however, a longer-duration study is needed for conclusive evidence. Our proposed study will investigate the effects of a 24-week high-fat diet with almonds (15% calories from almonds) on circulating iron concentrations in C57BL/6 mice. We hypothesize this treatment will significantly improve iron status compared to high-fat and low-fat diets. We will also investigate whether this intake of almonds can mitigate aging-related AI in C57BL/6 mice, a frequently used model in aging research. We will further probe underlying mechanisms that may influence these effects, including changes in gut microbiota composition, hepcidin concentrations, and the antioxidant system in RBCs. If our hypotheses are borne out, we will demonstrate the potential of almonds as a dietary approach to mitigating AI. Furthermore, this work would be the first to elucidate the contributions of gut microbiota and RBC antioxidant system in mitigating AI.

项目摘要/摘要 炎症贫血（AI）是第二大流行的贫血形式。它是由慢性炎症引起的 与癌症和类风湿关节炎等衰老和慢性疾病有关。而患有人工智能的人 足够的身体铁，由于蛋白质肝素浓度升高而增加的隔离导致 红细胞合成的循环铁不足。 AI也因破坏红血而加剧了 由于炎症引起的巨噬细胞细胞（RBC）。不幸的是，当前的疗法，包括输血， 不要降低肝素浓度升高；此外，输血会增加铁的风险， 会导致不良影响。在开发靶向肝素的实验药物时，它们的长期 术语不利影响尚不清楚，需要新的非药物方法。我们的长期目标是 确定减轻AI的饮食方法。消耗杏仁可能会通过不同的机制来减轻AI； 其中包括（i）减少炎症，（ii）改变肠道微生物组组成和（iii）改进 RBC通过增加其维生素E含量的鲁棒性，从而保护它们免受氧化损害。在这个 拟议的R15研究，我们将检验总体假设，即杏仁消耗将改善铁的状态 炎症状态，使用肥胖和衰老小鼠。我们选择了这些鼠标模型，因为这两个条件均为 与炎症相关，肝素增加和铁状态标志物受损。我们的初步为期8周 使用肥胖的小鼠模型的研究提供了暗示性的证据，表明常规杏仁摄入量会降低肝素 并提高了血浆中的铁浓度；但是，需要进行更长时间的研究才能确定证据。 我们提出的研究将研究24周高脂饮食的杏仁的影响（来自 杏仁）C57BL/6小鼠的循环铁浓度。我们假设这种治疗将大大显着 与高脂和低脂饮食相比，提高铁状态。我们还将调查这种杏仁的摄入量是否 可以减轻C57BL/6小鼠中与衰老相关的AI，这是衰老研究中常用的模型。我们将进一步探测 可能影响这些影响的基本机制，包括肠道菌群组成的变化， 肝素浓度和RBC中的抗氧化剂系统。如果我们的假设出现了，我们将 证明杏仁是减轻AI的饮食方法的潜力。此外，这项工作将是 第一个阐明肠道微生物群和RBC抗氧化系统在缓解AI中的贡献的是。